Cited by 6,670Bone Metabolism and DiseasesBone health and osteoporosis researchBone and Dental Protein Studies

The DOI matches its Crossref record; 77 of the 77 references it cites were found in a registry or an index.

Osteoclast differentiation and activation

Boyle, William J., Simonet, W. Scott, Lacey, David L.·2003·Nature

Open this paper in CoChat — free account

Abstract

Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.

Integrity signals

Registry

Crossref · 10.1038/nature01658

Cites

77 of 77 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Self-citation
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130
Self-citation
Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
Bone Resorption by Osteoclasts
Teitelbaum, S. L. (2000) · Science · doi:10.1126/science.289.5484.1504 · Cited by 3,962
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Self-citation
Induction and Activation of the Transcription Factor NFATc1 (NFAT2) Integrate RANKL Signaling in Terminal Differentiation of Osteoclasts
Takayanagi, H., Kim, S., Koga, T., Nishina, H., Isshiki, M., Yoshida, H., Saiura, A., Isobe, M., Yokochi, T., Inoue, J.-I., et al. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00369-6 · Cited by 2,701
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
Self-citation
NF-κB in cancer: from innocent bystander to major culprit
Karin, M., Cao, Y., Greten, F. R., & Li, Z. (2002) · Nature reviews. Cancer · doi:10.1038/nrc780 · Cited by 2,476
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290
Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand.
Kong, Y.-Y., Feige, U., Sarosi, I., Bolon, B., Tafuri, A., Morony, S., Capparelli, C., Li, J., Elliott, R., McCabe, S., et al. (1999) · Nature · doi:10.1038/46303 · Cited by 1,856
Self-citation

Flagged first, then by citations

Show all 77 references

Sorted by citations

Items 301–400 of 1,034

Inflammatory monocytes and Fcγ receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice
Seeling, M., Hillenhoff, U., David, J. P., Schett, G. A., Tuckermann, J. P., Lux, A., & Nimmerjahn, F. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301001110 · Cited by 174
“Upon recruitment of myeloid precursors of osteoclasts to the inflamed joint, the proinflammatory milieu supports the development of mature osteoclasts that start to resorb bone and are ultimately responsible for joint destruction (1, 24).”
Background
TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation
Zha, L., Li, H., Liang, Y., Qin, H., Yu, B., Chang, L., & Li, X. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.03.080 · Cited by 172
Asynchronous nuclear cycles in multinucleated Plasmodium falciparum facilitate rapid proliferation
Klaus, S., Binder, P., Kim, J., Machado, M., Funaya, C., Schaaf, V., Klaschka, D., Kudulyte, A., Cyrklaff, M., Laketa, V., et al. (2022) · Science Advances · doi:10.1126/sciadv.abj5362 · Cited by 165
“Nevertheless, multinucleated cells can be readily found throughout the eukaryotic tree of life ( 1 ) and can be seen in several unicellular organisms ( 2 ), early embryos of insects ( 3 ), during plant seed development ( 4 ), or in osteoclasts and myotubes of vertebrates ( 5 , 6 ).”
Background
Actin cytoskeletal organisation in osteoclasts: A model to decipher transmigration and matrix degradation
Saltel, F., Chabadel, A., Bonnelye, E., & Jurdic, P. (2008) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2008.01.001 · Cited by 170
RANKL, RANK, osteoprotegerin: key partners of osteoimmunology and vascular diseases
Baud’huin, M., Lamoureux, F., Duplomb, L., Rédiní, F., & Heymann, D. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7104-0 · Cited by 177
Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice
Halade, G. V., Jamali, A. E., Williams, P. J., Fajardo, R. J., & Fernandes, G. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.09.014 · Cited by 169
“In addition, osteoblasts produce receptor activator of nuclear factor-κβ ligand (RANKL) and osteoprotegerin (OPG), two critical factors in osteoclast differentiation (Boyle et al., 2003).”
Osteoclast‐specific Dicer gene deficiency suppresses osteoclastic bone resorption
Mizoguchi, F., Izu, Y., Hayata, T., Hemmi, H., Nakashima, K., Nakamura, T., Kato, S., Miyasaka, N., Ezura, Y., & Noda, M. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22228 · Cited by 170
Osteotropic cancers: From primary tumor to bone
Buijs, J. T., & van der Pluijm, G. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.05.044 · Cited by 175
Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression
Zeng, X., He, L., Wang, S., Wang, K., Yue-yang, Z., Tao, L., Li, X., & Liu, S. (2015) · Acta Pharmacologica Sinica · doi:10.1038/aps.2015.85 · Cited by 170
Osteoclast Multinucleation: Review of Current Literature
Kodama, J., & Kaito, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165685 · Cited by 177
“They differentiate upon exposure to macrophage colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), which are presented by osteoblasts and osteocytes [1].”
Background
Thyroid Hormone Actions in Cartilage and Bone
Williams, G. R. (2012) · European Thyroid Journal · doi:10.1159/000345548 · Cited by 174
Immunopathology of psoriasis and psoriatic arthritis
Veale, D., Ritchlin, C., & FitzGerald, O. (2005) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2004.031740 · Cited by 172
“53 Specifically, RANKL, expressed on the surface of osteoblasts and stromal cells in the bone marrow and infiltrating T lymphocytes and synoviocytes in the inflamed joint, binds to RANK, a cell associated TNF receptor related protein.”
Background
Gene array analysis of Wnt-regulated genes in C3H10T1/2 cells
Jackson, A. M., Vayssière, B., Garcia, T., Newell, W., Baron, R., Roman‐Roman, S., & Rawadi, G. (2005) · Bone · doi:10.1016/j.bone.2005.01.007 · Cited by 169
Inhibition of Hormone and Cytokine-stimulated Osteoclastogenesis and Bone Resorption by Interleukin-4 and Interleukin-13 Is Associated with Increased Osteoprotegerin and Decreased RANKL and RANK in a STAT6-dependent Pathway
Palmqvist, P., Lundberg, P., Persson, E., Johansson, A., Lundgren, I., Lie, A., Conaway, H. H., & Lerner, U. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510160200 · Cited by 167
Parathyroid Hormone Controls Receptor Activator of NF-κB Ligand Gene Expression via a Distant Transcriptional Enhancer
Fu, Q., Manolagas, S., & O'Brien, C. A. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00356-06 · Cited by 165
“It has been established during the last few years that osteoclasts are derived from hematopoietic precursors in a process that is strictly dependent on the interaction of the receptor activator of NF- B ligand (RANKL), a membrane-bound member of the tumor necrosis factor (TNF) family of cytokines (Tnfsf11) produced by…”
Background
HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE
Zhou, Z., Han, J.-Y., Xi, C.-X., Xie, J.-X., Feng, X., Wang, C.-Y., Mei, L., & Xiong, W.-C. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080234 · Cited by 160
Glucose metabolism in bone
Karner, C. M., & Long, F. (2017) · Bone · doi:10.1016/j.bone.2017.08.008 · Cited by 163
Targeting strategies for bone diseases: signaling pathways and clinical studies
Xu, H., Wang, W., Liu, X., Huang, W. H., Chen, Z., Xu, Y., Yang, H., Bai, J., & Geng, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01467-8 · Cited by 177
“As a transcription factor, NFATc1 promotes osteoclastogenesis by upregulating the expression of resorption-related genes, such as cathepsin K, matrix metalloproteinase 9 (MMP9), tartrateresistant acid phosphatase (TRAP), and acid phosphatase 5 (Acp5).(25,26) Apart from RANK/RANKL and M-CSF, other factors have been rev…”
Background
Targeted therapies for non-small cell lung cancer
Dempke, W. C. M., Sütö, T., & Reck, M. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.10.012 · Cited by 165
“Recent research has identified the essential cytokine system for the regulation of bone remodelling in health and in disease [129].”
Background
Macrophage Infiltration Predicts a Poor Prognosis for Human Ewing Sarcoma
Fujiwara, T., Fukushi, J., Yamamoto, S., Matsumoto, Y., Setsu, N., Oda, Y., Yamada, H., Okada, S., Watari, K., Ono, M., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.05.034 · Cited by 165
Identification of cell cycle–arrested quiescent osteoclast precursors in vivo
Mizoguchi, T., Muto, A., Udagawa, N., Arai, A., Yamashita, T., Hosoya, A., Ninomiya, T., Nakamura, H., Yamamoto, Y., Kinugawa, S., et al. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200806139 · Cited by 166
“RANKL-defi cient (RANKL / ) mice also exhibit severe osteopetrosis because of a lack of osteoclasts ( Kong et al., 1999 ; Suda et al., 1999 ; Arron and Choi, 2000 ; Hofbauer et al., 2000 ; Takahashi et al., 2002 ; Boyle et al., 2003 ).”
Origins, Biology, and Diseases of Tissue Macrophages
Cox, N., Pokrovskii, M. V., Vicario, R., & Geissmann, F. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-111748 · Cited by 171
Protein tyrosine phosphatases in health and disease
Hendriks, W. J. A. J., Elson, A., Harroch, S., Pulido, R., Stoker, A. W., & den Hertog, J. (2012) · FEBS Journal · doi:10.1111/febs.12000 · Cited by 164
Regulation of apoptosis in osteoclasts and osteoblastic cells
Xing, L., & Boyce, B. F. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.072 · Cited by 171
Relationship between pulmonary emphysema and osteoporosis assessed by CT in patients with COPD.
Ohara, T., Hirai, T., Muro, S., Haruna, A., Terada, K., Kinose, D., Marumo, S., Ogawa, E., Hoshino, Y., Niimi, A., et al. (2008) · Chest · doi:10.1378/chest.07-3054 · Cited by 169
Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1‐targeting miRNA‐92a‐1‐5p
Yu, L., Sui, B., Fan, W., Lei, L., Zhou, L., Liu, Y., Diao, Y., Zhang, Y., Li, Z., Liu, J., et al. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12056 · Cited by 166
“RANKL has been reported to play a crucial role in osteoclast differentiation (Boyle et al., 2003).”
Background
Role of nuclear factor‐κB in the immune system and bone
Jimi, E., & Ghosh, S. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00329.x · Cited by 167
“Bone, despite its hard structure, is actually in a constant state of dynamic turnover known as bone remodeling (4, 5).”
Background
Nrf2 Negatively Regulates Osteoblast Differentiation via Interfering with Runx2-dependent Transcriptional Activation
Hinoi, E., Fujimori, S., Wang, L., Hojo, H., Uno, K., & Yoneda, Y. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600603200 · Cited by 162
Staphylococcus aureus Protein A Plays a Critical Role in Mediating Bone Destruction and Bone Loss in Osteomyelitis
Widaa, A., Claro, T., Foster, T. J., O’Brien, F. J., & Kerrigan, S. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040586 · Cited by 166
Osteoimmunology: Interactions of the Immune and Skeletal Systems
Rho, J., Takami, M., & Choi, Y. (2004) · Molecules and Cells · doi:10.1016/s1016-8478(23)12997-9 · Cited by 159
RNA Sensing by Gut Piezo1 Is Essential for Systemic Serotonin Synthesis
Sugisawa, E., Takayama, Y., Takemura, N., Kondo, T., Hatakeyama, S., Kumagai, Y., Sunagawa, M., Tominaga, M., & Maruyama, K. (2020) · Cell · doi:10.1016/j.cell.2020.06.022 · Cited by 161
Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis
Kelchtermans, H., Geboes, L., Mitera, T., Huskens, D., Leclercq, G., & Matthys, P. (2008) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2007.086066 · Cited by 164
Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives
Terkawi, M. A., Matsumae, G., Shimizu, T., Takahashi, D., Kadoya, K., & Iwasaki, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031786 · Cited by 174
“The duration of the resorption phase is limited and characterized by recruiting osteoclast precursors to the remodeling site, followed by the reversal phase that is characterized by the disappearance of osteoclasts that are replaced by osteoblasts for bone formation [1,3].”
Background
Novel functions for NFκB: inhibition of bone formation
Krum, S. A., Chang, J., Miranda‐Carboni, G. A., & Wang, C. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.133 · Cited by 160
“Receptor activator of nuclear factor κB ligand (RANKL; also known as TNF ligand superfamily, member 11) is an essential cytokine in osteoclastogenesis, along with macrophage colony stimulating factor (M-CSF)”
Background
Convergent signaling by acidosis and receptor activator of NF-κB ligand (RANKL) on the calcium/calcineurin/NFAT pathway in osteoclasts
Komarova, S. V., Pereverzev, A., Shum, J., Sims, S. M., & Dixon, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406874102 · Cited by 161
Regulatory mechanism of NFATc1 in RANKL‐induced osteoclast activation
Song, I., Kim, J. H., Kim, K., Jin, H. M., Youn, B. U., & Kim, N. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.06.047 · Cited by 163
“Receptor activator of NF-jB ligand (RANKL) plays a key role in osteoclast differentiation, fusion, and activation [3].”
Background
Interleukin‐34 is expressed by giant cell tumours of bone and plays a key role in RANKL‐induced osteoclastogenesis
Baud’huin, M., Renault, R., Charrier, C., Riet, A., Moreau, A., Brion, R., Gouin, F., Duplomb, L., & Heymann, D. (2010) · The Journal of Pathology · doi:10.1002/path.2684 · Cited by 160
RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives
Infante, M., Fabi, A., Cognetti, F., Gorini, S., Caprio, M., & Fabbri, A. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-1001-2 · Cited by 180
“tartrate-resistant acid phosphatase) [2, 8].”
Effect of Calcium Ion Concentrations on Osteogenic Differentiation and Hematopoietic Stem Cell Niche-Related Protein Expression in Osteoblasts
Nakamura, S., Matsumoto, T., Sasaki, J., Egusa, H., Lee, K. Y., Nakano, T., Sohmura, T., & Nakahira, A. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2009.0337 · Cited by 158
“5 The acid produced by osteoclasts in this process enhances mineralized bone desorption; thereby, the amount of calcium (Ca) in the local bone-remodeling region changes depending on its degree.”
MicroRNA-124 regulates osteoclast differentiation
Lee, Y., Kim, H. J., Park, C., Kim, Y., Lee, H., Kim, J., & Kim, H. (2013) · Bone · doi:10.1016/j.bone.2013.07.007 · Cited by 159
“Osteoclasts, originated from the monocyte/macrophage precursors, are specialized cells for bone resorption [1].”
Background
Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: Efficacy and safety results from a randomized open-label study
Roux, C., Hofbauer, L. C., Ho, P., Wark, J. D., Zillikens, M. C., Fahrleitner‐Pammer, A., Hawkins, F. G., Micaëlo, M., Minisola, S., Παπαϊωάννου, Ν., et al. (2013) · Bone · doi:10.1016/j.bone.2013.10.006 · Cited by 158
“Denosumab is a fully human monoclonal antibody against RANKL, a cytokine that is an essential mediator for osteoclast formation, function, and survival [7].”
Background
Macrophages and Bone Remodeling
Weivoda, M. M., & Bradley, E. W. (2023) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4773 · Cited by 166
“More specifically, inflammatory mediators produced by macrophages drive enhanced expression of stromal and lymphocyte RANKL, thus increasing osteoclastogenesis.((166-168)) Inhibitors targeting inflammatory mediators, including TNF-α and IL-1, attenuate enhanced osteoclast activity and bone loss associated with periodo…”
Background
Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins
Luegmayr, E., Glantschnig, H., Wesolowski, G. A., Gentile, M. A., Fisher, J. E., Rodan, G. A., & Reszka, A. A. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401399 · Cited by 162
“OCL survival primarily depends not only on antiapoptotic signaling mediated by M-CSF but also other cytokines like RANKL and TNFa.64,65 A very recent study demonstrated that MBCD treatment reduced survival and activity of in vitro generated OCL.21 This correlated with impairment of RANKLinduced signaling.”
Background
Androgen deprivation therapy for prostate cancer: new concepts and concerns
Smith, M. R. (2007) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e32814db88c · Cited by 157
Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and Cbfa1 expression
Hsieh, T.-P., Sheu, S.-Y., Sun, J., Chen, M., & Liu, M.-H. (2009) · Phytomedicine · doi:10.1016/j.phymed.2009.08.007 · Cited by 157
“RANKL represents the osteoblasts-derived factor required for osteoclast formation, whereas OPG blocks these effects and prevents bone resorption in the various microenvironments (Boyle et al. 2003).”
Background
Bone Morphogenetic Protein 2 and Retinoic Acid Accelerate in Vivo Bone Formation, Osteoclast Recruitment, and Bone Turnover
Cowan, C. M., Aalami, O., Shi, Y.-Y., Chou, Y., Aparici, C. M., Thomas, R., Quarto, N., Nacamuli, R. P., Contag, C. H., Wu, B. M., et al. (2005) · Tissue Engineering · doi:10.1089/ten.2005.11.645 · Cited by 156
“45 The presence of large multinucleated cells in combination with positive CTR staining, a marker for osteoclast phenotype, 46,47 in defects that received either unseeded and cell-seeded scaffolds indicates that circulating or local host osteoclasts invaded the scaffolds that had been prestimulated…”
Targeting Syk as a treatment for allergic and autoimmune disorders
Wong, B. R., Grossbard, E. B., Payan, D. G., & Masuda, E. S. (2004) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.13.7.743 · Cited by 156
The regulation of osteoclast function and bone resorption by small GTPases
Itzstein, C., Coxon, F. P., & Rogers, M. J. (2011) · Small GTPases · doi:10.4161/sgtp.2.3.16453 · Cited by 160
“Osteoclasts are large, multinucleated, motile cells that are formed by the fusion of hematopoietic cells of the monocyte/macrophage lineage.(1,2) They are the only cells in the body that are able to degrade (resorb) extracellular bone matrix, a process that is required for bone morphogenesis during development, for th…”
Background
CD44 and β3 Integrin Organize Two Functionally Distinct Actin-based Domains in Osteoclasts
Chabadel, A., Bañon-Rodríguez, I., Cluet, D., Rudkin, B. B., Wehrle-Haller, B., Genot, E., Jurdic, P., Anton, I. M., & Saltel, F. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-04-0378 · Cited by 154
“Recombinant human RANK-L and human M-CSF were produced as described previously (Destaing et al., 2003).”
BackgroundInfluential
Osteoclast differentiation requires TAK1 and MKK6 for NFATc1 induction and NF-κB transactivation by RANKL
Huang, H., Ryu, J., Ha, J., Chang, E.-J., Kim, H. J., Kim, H.-M., Kitamura, T., Lee, Z. H., & Kim, H. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401882 · Cited by 156
“For example, ERK was shown to have an antiapoptotic role but no resorptionactivating effect in mature Ocs.7 In the Oc differentiation process, the activity of ERKs was implicated for negative roles.8 It was suggested that JNK participates to Oc differentiation by playing a role in RANKL induction of NFATc1 expression…”
BackgroundMethodInfluential
Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production
He, X., Andersson, G., Lindgren, U., & Li, Y. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.09.053 · Cited by 156
The role of osteoclast differentiation and function in skeletal homeostasis
Ikeda, K., & Takeshita, S. (2015) · The Journal of Biochemistry · doi:10.1093/jb/mvv112 · Cited by 160
“dissolving both the inorganic and organic components of the matrix, by secreting protons and collagenolytic enzymes (5, 12), which is an energy-demanding process.”
Background
Physiology of Parathyroid Hormone
Goltzman, D. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.07.003 · Cited by 154
Osteoprotegerin: Multiple partners for multiple functions
Baud’huin, M., Duplomb, L., Teletchea, S., Lamoureux, F., Ruiz-Velasco, C., Maillasson, M., Redini, F., Heymann, M.-F., & Heymann, D. (2013) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2013.06.001 · Cited by 153
“The binding of OPG to RANKL prevents the interaction of RANKL for RANK expressed on the cell surface of osteoclast precursors, and thus inhibits the formation of osteoclasts (Boyle et al. 2003).”
Background
Ferric ion could facilitate osteoclast differentiation and bone resorption through the production of reactive oxygen species
Peng, J., Xu, Y. J., Zhang, Z. L., Li, K., Li, B., Zhang, W., & Yang, H. (2012) · Journal of Orthopaedic Research® · doi:10.1002/jor.22133 · Cited by 155
“This action can be blocked by osteoprotegerin (OPG), a soluble decoy receptor that competes with RANK for binding to RANKL on osteoblasts and lymphocytes.(41) It has been shown that ROS could induce the upregulation of RANKL mRNA and protein in osteoblasts, but they had little effect on OPG.”
Background
Pathophysiology and New Strategies for the Treatment of Legg-Calvé-Perthes Disease
Kim, H. K. W. (2012) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.j.01834 · Cited by 153
New understanding and treatments for osteoporosis
Mazziotti, G., Bilezikian, J. P., CANALIS, E. M., Cocchi, D., & Giustina, A. (2011) · Endocrine · doi:10.1007/s12020-011-9570-2 · Cited by 151
Cancer-induced bone pain: Mechanisms and models
Lozano‐Ondoua, A. N., Symons-Liguori, A. M., & Vanderah, T. W. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.08.003 · Cited by 156
Infection and Medication-related Osteonecrosis of the Jaw
Katsarelis, H., Shah, N., Dhariwal, D. K., & Pazianas, M. (2015) · Journal of Dental Research · doi:10.1177/0022034515572021 · Cited by 151
“Denosumab decreases bone turnover by inhibiting the binding of RANKL in the cell membrane of osteoclasts and osteoclast precursor cells (Ginhoux and Jung 2014), thus affecting the number and function of osteoclasts (Boyle et al. 2003) and producing almost complete suppression of osteoclastogenesis— when given subcutan…”
Background
AMP kinase acts as a negative regulator of RANKL in the differentiation of osteoclasts
Lee, Y., Kim, Y.-S., Lee, S.-Y., Kim, G.-H., Kim, B., Lee, S., Lee, K., Kim, G.-S., Kim, S., & Koh, J. (2010) · Bone · doi:10.1016/j.bone.2010.08.001 · Cited by 154
“responsible for bone resorption [1].”
BackgroundInfluential
Myeloma bone disease: from biology findings to treatment approaches
Terpos, E., Ntanasis‐Stathopoulos, I., & Dimopoulos, M. A. (2019) · Blood · doi:10.1182/blood-2018-11-852459 · Cited by 151
Insights and implications of sexual dimorphism in osteoporosis
Zhang, Y., Xie, N., Sun, X., Nice, E. C., Liou, Y., Huang, C., Zhu, H., & Shen, Z. (2024) · Bone Research · doi:10.1038/s41413-023-00306-4 · Cited by 164
“82 Osteocytes, osteoblasts, and osteoclasts are all crucial components for maintaining normal bone function, and any disruption in their homeostasis underlies the pathogenesis of osteoporosis.”
Background
Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells
Grigoriadis, A. E., Kennedy, M., Bozec, A., Brunton, F., Stenbeck, G., Park, I.-H., Wagner, E. F., & Keller, G. M. (2010) · Blood · doi:10.1182/blood-2009-07-234690 · Cited by 151
Vitamin D and gene networks in human osteoblasts
van de Peppel, J., & van Leeuwen, J. P. T. M. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00137 · Cited by 151
“…osteoclast stimulating factors RANKL and M-CSF which upon binding to its receptors (RANK and c-Fms, respectively) induce differentiation of osteoclast progenitors and fusion of mononuclear cells into multinucleated tartrate-resistant acid phosphatase positive osteoclasts (Boyle et al., 2003).”
Background
Preclinical studies and clinical evaluation of compounds from the genus Epimedium for osteoporosis and bone health
Indran, I. R., Liang, R. L. Z., Min, T., & Yong, E. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.01.015 · Cited by 150
Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts
Boyce, B. F. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1885 · Cited by 153
NF-κB p100 limits TNF-induced bone resorption in mice by a TRAF3-dependent mechanism
Yao, Z., Xing, L., & Boyce, B. F. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38716 · Cited by 151
Periodontitis and type II diabetes: a two-way relationship
Chee, B., Park, B., & Bartold, P. M. (2013) · International Journal of Evidence-Based Healthcare · doi:10.1111/1744-1609.12038 · Cited by 155
Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production
Koga, Y., Tsurumaki, H., Aoki‐Saito, H., Sato, M., Yatomi, M., Takehara, K., & Hisada, T. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20061346 · Cited by 152
Ginseng-derived exosome-like nanovesicles extracted by sucrose gradient ultracentrifugation to inhibit osteoclast differentiation
Seo, K., Yoo, J. H., Kim, J., Min, S. J., Heo, D. N., Kwon, I. K., & Moon, H. (2023) · Nanoscale · doi:10.1039/d2nr07018a · Cited by 149
The realm of vitamin K dependent proteins: Shifting from coagulation toward calcification
Willems, B. A. G., Vermeer, C., Reutelingsperger, C. P. M., & Schurgers, L. J. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300743 · Cited by 149
Osteoclast-Derived Coupling Factors in Bone Remodeling
Henriksen, K., Karsdal, M. A., & Martin, T. J. (2013) · Calcified Tissue International · doi:10.1007/s00223-013-9741-7 · Cited by 146
“Although communication seemed likely to occur in both directions [10, 11], essentially nothing was known of the generation and activity in remodeling through the reverse pathway, through which the osteoblast lineage might be programmed to replace the bone that has been resorbed.”
Background
Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood
Sørensen, M. G., Henriksen, K., Schaller, S., Henriksen, D. B., Nielsen, F. C., Dziegiel, M. H., & Karsdal, M. A. (2006) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-006-0725-9 · Cited by 143
IGF-I Receptor Is Required for the Anabolic Actions of Parathyroid Hormone on Bone
Wang, Y., Nishida, S., Boudignon, B. M., Burghardt, A. J., Elalieh, H. Z., Hamilton, M. M., Majumdar, S., Halloran, B. P., Clemens, T. L., & Bikle, D. D. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070517 · Cited by 147
Acute and Stress-related Injuries of Bone and Cartilage: Pertinent Anatomy, Basic Biomechanics, and Imaging Perspective
Pathria, M. N., Chung, C. B., & RESNICK, D. L. (2016) · Radiology · doi:10.1148/radiol.16142305 · Cited by 150
“Osteoclasts are responsible for acidification of the resorption compartment, dissolution of the mineral component of the bone matrix, and digestion of the proteinaceous matrix (4,6).”
Background
Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapies: A Review
Bi, H., Chen, X., Gao, S., Yu, X., Xiao, J., Zhang, B., Liu, X., & Dai, M. (2017) · Frontiers in Medicine · doi:10.3389/fmed.2017.00234 · Cited by 146
“Lancet Diabetes Endocrinol (2017) 5(7):513–23.”
Background
Pathogenic mechanisms of glucocorticoid-induced osteoporosis
Chen, M., Fu, W., Xu, H., & Liu, C.-J. (2023) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2023.03.002 · Cited by 146
Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting
Chiarini, F., Lonetti, A., Evangelisti, C., Buontempo, F., Orsini, E., Evangelisti, C., Cappellini, A., Neri, L. M., McCubrey, J. A., & Martelli, A. M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.08.015 · Cited by 154
Osteoblasts induce Ca 2+ oscillation-independent NFATc1 activation during osteoclastogenesis
Kuroda, Y., Hisatsune, C., Nakamura, T., Matsuo, K., & Mikoshiba, K. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0800642105 · Cited by 148
“S development requires a delicate balance between bone formation by osteoblasts and resorption by osteoclasts, and imbalances in bone remodeling cause various types of skeletal disorders (1, 2).”
Background
Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies
Jorcyk, C. L., Tawara, K., & Jorcyk, C. L. (2011) · Cancer Management and Research · doi:10.2147/cmr.s18101 · Cited by 153
T cells support osteoclastogenesis in an in vitro model derived from human multiple myeloma bone disease: the role of the OPG/TRAIL interaction
Colucci, S. C., Brunetti, G., Rizzi, R., Zonno, A., Mori, G., Colaianni, G., Prete, D. D., Faccio, R., Liso, A., Capalbo, S. F., et al. (2004) · Blood · doi:10.1182/blood-2004-02-0474 · Cited by 146
“Osteoclastogenesis is positively or negatively regulated by a complex signaling system, that involves the receptor activator of nuclear factor (NF)-kB (RANK), osteoprotegerin (OPG) and receptor activator of nuclear factor (NF)-kB ligand (RANKL), all belonging to the tumor necrosis factor (TNF) family.(12) The osteocla…”
Background
Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton Pump That Mediates Extracellular Acidification in Bone Resorption
Wu, H., Xu, G., & Li, Y. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081239 · Cited by 145
“day3 osteoclasts to rule out the contributions of mono- and di-nucleated pre-osteoclasts, which may also participate in the formation of resorption lacunae of small sizes.((2)) Osteoclasts from sh-d2-3, sh-LacZ, or UT produced ;13.”
Background
Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD
Ciucci, T., Ibáñez, L., Boucoiran, A., Birgy, É., Pène, J., Abou‐Ezzi, G., Arab, N., Rouleau, M., Hébuterne, X., Yssel, H., et al. (2014) · Gut · doi:10.1136/gutjnl-2014-306947 · Cited by 148
RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss
Hu, Y., Li, X., Zhi, X., Cong, W., Huang, B., Chen, H., Wang, Y., Li, Y., Wang, L., Fang, C., et al. (2021) · EMBO Reports · doi:10.15252/embr.202152481 · Cited by 147
“Osteoclasts are specialized multinucleated cells derived from the monocyte – macrophage hematopoietic lineage and are responsible for resorption of bone matrix (Boyle et al , 2003).”
A Multifunctional Composite Hydrogel That Rescues the ROS Microenvironment and Guides the Immune Response for Repair of Osteoporotic Bone Defects
Chen, Q., Li, J., Han, F., Meng, Q., Wang, H., Wei, Q., Li, Z., Li, F., Xie, E., Qin, X., et al. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202201067 · Cited by 146
Effects of resistance and aerobic exercise on physical function, bone mineral density, OPG and RANKL in older women
Marques, E. A., Wanderley, F. A. C., Machado, L. J., Sousa, F., Viana, J. L., Moreira‐Gonçalves, D., Moreira, P. A. M., Mota, J. A. P. S., & Carvalho, J. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.02.005 · Cited by 143
“Although it is well known that OPG blocks the differentiation of preosteoclastic cells into osteoclasts by inhibiting the binding of RANK to RANKL and, consequently, reduces osteoclastic bone resorption (Boyle et al., 2003), not all mechanical stimulation studies have shown an increase in OPG with osteoblast stimulati…”
Background
Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies
Hamerman, D. (2005) · QJM · doi:10.1093/qjmed/hci077 · Cited by 146
Bioactive behavior of silicon substituted calcium phosphate based bioceramics for bone regeneration
Khan, A. F., Saleem, M., Afzal, A., Ali, A., Khan, A. R., & Khan, A. R. (2013) · Materials Science and Engineering C · doi:10.1016/j.msec.2013.11.013 · Cited by 142
“The presence of calcium phosphates distinguishes bone from other hard tissues like shell, chitin and enamel [3].”
Background
The role of RANK ligand/osteoprotegerin in rheumatoid arthritis
Geusens, P. (2012) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x12438080 · Cited by 145
“RANKL binds to the RANK receptor on the surface of osteoclast precursors and mature osteoclasts, resulting in differentiation and activation of osteoclasts [Boyle et al. 2003].”
Background
Imaging Features and Management of Stress, Atypical, and Pathologic Fractures
Marshall, R. A., Mandell, J. C., Weaver, M. J., Ferrone, M. L., Sodickson, A. D., & Khurana, B. (2018) · Radiographics · doi:10.1148/rg.2018180073 · Cited by 142
The Biology of the Cytolethal Distending Toxins
Guerra, L., Cortes-Bratti, X., Guidi, R., & Frisan, T. (2011) · Toxins · doi:10.3390/toxins3030172 · Cited by 153
“This process is negatively regulated by Osteoprotegerin (OPG), which acts as a decoy receptor for RANKL, preventing its interaction with RANK and osteoclast maturation (reviewed in [80]).”
Background
Longevity and Lineages: Toward the Integrative Biology of Degenerative Diseases in Heart, Muscle, and Bone
Chien, K. R., & Karsenty, G. (2005) · Cell · doi:10.1016/j.cell.2005.02.006 · Cited by 143
“Parathyroid hormone (PTH) s binds to a specific receptor present on osteoblasts and d upregulates RANKL expression and decreases OPG exn pression (Boyle et al., 2003), resulting in an increase in g osteoclast differentiation.”
Signaling Pathways Involved in Osteogenesis and Their Application for Bone Regenerative Medicine
Hayrapetyan, A., Jansen, J. A., & van den Beucken, J. J. J. P. (2014) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2014.0119 · Cited by 146
“3,8,9 Current strategies in bone regenerative medicine are focused particularly on the biomaterial characteristics for the generation of material-and cell-based bone substitutes (al-loplasts) that trigger the endogenous healing capacity of the human body.”
Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: relevance for arthritis
Lee, J.-H., Kim, B.-J., Jin, W. J., Kim, H., Ha, H., & Lee, Z. H. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1353-6 · Cited by 143
“Background Osteoclasts, multinucleated bone-resorbing cells, are essential mediators of inflammatory bone erosion and are derived from monocyte/macrophage lineage precursor cells through the action of RANKL, a key factor for osteoclastogenesis [1].”
The microbiota-gut-bone axis and bone health
Tu, Y., Yang, R., Xu, X., & Zhou, X. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mr0321-755r · Cited by 144
The Multiple Roles of Osteoclasts in Host Defense: Bone Remodeling and Hematopoietic Stem Cell Mobilization
Kollet, Ó., Dar, A., & Lapidot, T. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141631 · Cited by 141
RANKL/RANK—beyond bones
Hanada, R., Hanada, T., Sigl, V., Schramek, D., & Penninger, J. M. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0749-z · Cited by 147
Interleukin-6 Inhibits Receptor Activator of Nuclear Factor κB Ligand-Induced Osteoclastogenesis by Diverting Cells into the Macrophage Lineage: Key Role of Serine727 Phosphorylation of Signal Transducer and Activator of Transcription 3
Duplomb, L., Baud’huin, M., Charrier, C., Berreur, M., Trichet, V., Blanchard, F., & Heymann, D. (2008) · Endocrinology · doi:10.1210/en.2007-1719 · Cited by 142
CircRNA_28313/miR-195a/CSF1 axis modulates osteoclast differentiation to affect OVX-induced bone absorption in mice
Chen, X., Ouyang, Z., Shen, Y., Liu, B., Zhang, Q., Wan, L., Yin, Z., Zhu, W., Li, S., & Peng, D. (2019) · RNA Biology · doi:10.1080/15476286.2019.1624470 · Cited by 139
“The critical cytokines, such as receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (CSF1), are required for differentiating progenitor cells into osteoclasts [4,5].”
Background
Postmenopausal Osteoporosis: The Role of Immune System Cells
Faienza, M. F., Ventura, A., Marzano, F., & Cavallo, L. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/575936 · Cited by 139
“Osteoprotegerin (OPG), a soluble decoy receptor secreted by OBs and bone marrow stromal cells, competes with RANK in binding to RANKL, preventing its osteoclastogenic effect [17].”

Authors: Boyle, W. J., Simonet, W. S., & Lacey, D. L.
Affiliations: Amgen (United States) (US)
Corresponding author: Boyle, William J.
ORCID: Boyle, William J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2003-05
Volume: 423
Issue: 6937
Pages: 337-342
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01658
OpenAlex: W2093252878
Cited by: 6,670
References: 77
Citations by year: 2026: 240 · 2025: 269 · 2024: 294 · 2023: 357 · 2022: 349 · 2021: 404 · 2020: 376 · 2019: 381 · 2018: 371 · 2017: 324 · 2016: 311 · 2015: 332 · 2014: 352 · 2013: 315 · 2012: 336
FWCI: 11.72
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
Keywords: osteoclasts, osteoclastogenesis, bone resorption, monocyte/macrophage lineage, bone matrix degradation, hormonal regulation of bone, osteoporosis
MeSH terms: Animals, Bone Resorption, Carrier Proteins, Cell Differentiation, Glycoproteins, Humans, Membrane Glycoproteins, Osteoclasts, Osteoporosis, Signal Transduction, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Osteoclast differentiation and activation

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks